Supporting Information
Resolving the Regioregularity of Poly(N-n-hexyl-N’phenylcarbodiimide) via Nitrogen-15 Labeling
Joseph D. DeSousa and Bruce M. Novak
Department of Chemistry and The Alan G MacDiarmid NanoTech Institute, The
University of Texas at Dallas, Richardson, Texas 75080-3021, United States
Contents
I.
II.
Characterization of Catalyst.
Synthesis of 15N-Enriched Reagents.
III.
Synthesis of 15N-Enriched (Thio)ureas.
IV.
Synthesis of 15N-Enriched Carbodiimides.
V.
VI.
VII.
Polymerizations of 15N-Enriched Carbodiimides.
15
N-NMR spectra and IR spectra of Polymers
References
S1
General Considerations
Materials. Heptanoyl chloride, benzoyl chloride, N-bromosuccimide, triethyl amine, and
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU),
Milwaukee, MI.
15
was purchased from Sigma-Aldrich,
N-ammonium chloride 99.9 % enriched was purchased from
Cambridge Isotopes, Cambridge MA. Solvents and reagents were purchased from the
Department of Chemistry, NCSU, Raleigh, NC.
NMR Spectroscopy. 1H-,
13
C-, and
15
N-NMR spectra were collected using a Varian
Mercury 400 spectrometer or Bruker 400 spectrometer using deuterated solvents from
Cambridge Isotope Labs, Cambridge, MA. The residual, undeutrated, solvent was used as
the internal reference for 1H- and
13
C-, while
15
N- used
15
N-Benzamide as an external
standard set to 0.00 ppm. Gadolinium(III) acetylacetonate hydrate was used as a
relaxation reagent for
15
N-NMR spectra of polymer at a concentration of 0.02 M in
CDCl3. Due to greater than 90 second relaxation times, the
15
N-NMR spectrum for
carbodiimide monomers were not collected.
Other Instrumentation. Solid-state infrared spectra was acquired with a Jasco FT-IR
fourier transform infrared spectrometer using a KBr pellet. For IR: s = strong peak, m =
medium, and w = weak peak.
Mass spectra were obtained at the NCSU Department of Chemistry Mass
Spectrometry Facility using 6210 LC-TOF mass spectrometer. For M-2 and M-4 mass
spectra were obtained using GC-MS QP2012 Plus Mass Spectrometer at the Dennis W.
Smith Jr. Research Group located in The University of Texas at Dallas.
S2
I. Catalysts:
Successful synthesis of trichloro-titanium(IV)-(2,2,2-trifluoroethoxide1, Cat-1,
and (R)-BINOL-titanium(IV)-diisopropoxide2, Cat-2, were conducted, confirmed, and
previously reported.
II. Synthesis of 15N-Enriched Reagents:
The synthesis of nitrogen-15 enriched amides were done using a modified
procedure by Zhang et al.3 The subsequent Hofmann Rearrangement was conducted
using a procedure outlined by Huang et al.4
15
N-Benzamide:
O
15
NH2
To a 250 ml round-bottom 40 ml of deionized water and 1.79 g (32.9 mmol, 1 eq.)
of
15
NH4Cl was added with a stir bar; agitation was started long enough to dissolve salt
and then turned off. Ethyl ether was added (100 ml) to the aqueous phase and allowed to
settle to form a bilayer followed by gentle addition of 7.61 ml (9.21g, 65.7 mmol, 2.0 eq.)
of benzoyl chloride. The bilayer was cooled to 0 °C with an ice bath. A solution of 11.06
g (197.1 mmol, 6.0 eq.) of KOH in 30 ml deionized water was chilled then added to the
aqueous phase through the organic phase using a glass pipette. The bilayer was left
undisturbed for 10 minutes followed by 10 minutes of mild stirring. The reaction was
S3
warmed to room temperature and stirred violently for 30 minutes. The organic phase was
washed with 50 ml of saturated sodium chloride solution and set aside. Additional
product was extracted with ethyl ether (3 X 100 ml) from the aqueous phase and
combined. The combined organic phase was dried with sodium sulfate and solvent was
removed via reduced pressure evaporation. Solids were washed with deionized water to
remove any remaining benzoate.
Yield: 1.31 g (10.8 mmol) white crystals, 66 %. FTIR (KBr pellet, cm-1): 3356 (s,
15
N-H str), 3188 (s, 15N-H str), 2956 (m, C-H alkyl), 2937 (m, C-H alkyl), 2870 (m, C-H
alkyl), 1653 (s, C=O), 1633 (w, 15N-H bend). 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.82
(Ar-H, J = 14.0 Hz, 2H, dt), 7.57 – 7.43 (Ar-H, 2H, m). 6.18 (15N-H, J = 72 Hz, 2H, d),
5.89 (15N-H, J = 72 Hz, 2H, d). 13C-NMR (100 MHz, CDCl3): 169.9, 133.6, 132.2, 128.8,
127.5
15
N-NMR (40.5 MHz, CDCl3): δ (ppm) 0.00. HRMS-ESI: Mtheroetical = 123.0571,
Msample = 123.0569, ΔM = -0.2 mmass units (-1.6 ppm), C7H715NO.
15
N-1-Heptanamide
O
15
NH 2
To a 500 ml round-bottom 75 ml of deionized water and 4.19 g (76.80 mmol, 1
eq.) of 15NH4Cl was added with a stir bar; agitation was started long enough to dissolve
salt and then turned off. Ethyl ether was added (150 ml) to the aqueous phase and
allowed to settle to form a bilayer followed by gentle addition of 23.78 ml (153.61 mmol,
S4
2.0 eq.) of heptanoyl chloride. The bilayer was cooled to 0 °C with an ice bath. A
solution of 25.9 g (460.8 mmol, 6.0 eq.) KOH in 40 ml deionized water was chilled then
added to the aqueous phase through the organic phase using a glass pipette. The bilayer
was left undisturbed for 10 minutes followed by 10 minutes of mild stirring. The reaction
was warmed to room temperature and stirred violently for 30 minutes. The organic phase
was separated from the aqueous phase and set aside. Additional product was extracted
with ethyl ether (3 X 100 ml) from the aqueous phase and combined the organic phase
and was dried with sodium sulfate. The ethyl ether was removed via reduced pressure
evaporation.
Yield: 7.47 g (57.4 mmol) white crystals, 74.7 %. FTIR (KBr pellet, cm-1): 3356
(s, 15N-H str), 3188 (s, 15N-H str), 2956 (m, C-H alkyl), 2937 (m, C-H alkyl), 2870 (m, CH alkyl), 1653 (s, C=O), 1633 (w,
15
N-H bend). 1H-NMR (400 MHz, CDCl3): δ (ppm)
5.57 (15N-H, J15N-1H = 88 Hz, 1H, d), 5.46 (15N-H, J15N-1H = 88 Hz, 1H, d), 2.22 (CH2CH2(CH2)3CH3, J = 8.0 Hz, 2H, t), 1.64 (-CH2CH2(CH2)3CH3, J = 7.2 Hz, 2H, p),
1.38 – 1.30 (-CH2CH2(CH2)3CH3, 6H, m), 0.89 (-CH2CH2(CH2)3CH3, J = 7.2 Hz, 3H, t).
13
C-NMR (100 MHz, CDCl3): δ (ppm) 176.0 (J13C-15N = 12.9 Hz), 36.1 (J13C-15N = 33.0
Hz), 31.7, 29.1, 25.7, 22.7, 14.2.
15
N-NMR (40.5 MHz, CDCl3): δ (ppm) 6.38. HRMS-
ESI: Mtheroetical = 131.1197, Msample = 131.1198, ΔM = 0.1 mmass units (0.7 ppm),
C7H1515NO.
S5
Methyl 15N-phenylcarbamate:
H
N
15
O
O
To a 1 L round-bottomed flask 500 ml of methanol, a magnetic stir bar, 2.57 g
(21.0 mmol, 1 eq) benzamide, and 3.75 g (21.0 mmol, 1 eq) N-bromosuccinimide (NBS)
was added. The flask was placed in an oil bath, stirring was started and 7.14 ml (7.27 g,
47.8 mmol, 2.27 eq) 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was added. The reaction
was refluxed for 15 minutes at which point a second addition of 3.75 g (21.0 mmol, 1 eq)
NBS was added slowly into the reaction, upon addition there is violent foaming that
quickly subsides. The reflux was allowed to continue for an additional 30 minutes.
Methanol is removed by reduced pressure evaporation and the residue is dissolved in 400
mL of ethyl acetate. The organic solution is washed with 6 N HCl (2 × 75 ml), followed
by 1.0 N NaOH (2 × 75 ml), saturated NaCl (2 X 50 ml), and finally dried over sodium
sulfate. The solvent is removed by reduced pressure evaporation and the crude product
purified by flash column chromatography (silica gel, ethyl acetate/hexane (1:1)). Further
purification done by crystallizing from hexanes.
Yield: 2.12 g (14.0 mmol) of a white crystals, 78 %. FTIR (KBr pellet, cm-1):
3296 (s,
15
N-H), 3126 (w, Ar-H), 3061 (m, Ar-H), 2952 (m, Alkyl-H), 1709 (s, C=O),
1599 (m, C=C). 1H-NMR (400 MHz, DMSOd6): δ (ppm) 9.64 (15N-H, J15N-1H = 91.2 Hz,
1H, d), 7.45 (Ar-H, J = 8.0 Hz, 2H, d), 7.27 (Ar-H, J = 7.6 Hz, 2H, t), 6.98 (Ar-H, J = 7.2
Hz, 2H, t), 3.66 (-CH3, 3H, s). 13C-NMR (100 MHz, DMSOd6): δ (ppm) 153.9 (J15N-13C =
S6
26.5 Hz), 139.1 (J15N-13C = 15.2 Hz), 128.8, 122.4, 118.1, 51.6.
15
N-NMR (40.5 MHz,
CDCl3): δ (ppm) 7.1. Mtheroetical = 153.0676, Msample = 153.0698, ΔM = 2.2 mmass units
(14.4 ppm), C8H915NO2.
Methyl 15N-(n-hexyl) carbamate:
15
H
N
O
O
To a 2 L round-bottomed flask 1500 ml of methanol, a magnetic stir bar, 7.00 g
(53.8 mmol, 1 eq.) 15N-heptanamide, and 9.57 g (53.8 mmol, 1 eq.) N-bromosuccinimide
(NBS) was added. The flask was placed in an hemispherical heating mantle, stirring was
started and 18.25 ml (18.6 g, 122.1 mmol, 2.27 eq.) 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) was added. The reaction was refluxed for 15 minutes at which point a second
addition of 9.57 g (53.8 mmol, 1 eq.) NBS was added slowly into the reaction, upon
addition there is violent foaming that quickly subsides. The reflux was allowed to
continue for an additional 30 minutes. Methanol is removed by reduced pressure
evaporation and the residue is dissolved in 400 mL of ethyl acetate. The organic solution
is washed with 6 N HCl (2 × 75 ml), followed by 1.0 N NaOH (2 × 75 ml), saturated
NaCl (1 X 50 ml), and finally dried over sodium sulfate. The solvent is removed by
reduced pressure evaporation and the crude product purified by flash column
chromatography (silica gel, ethyl acetate/hexane (3:1)). Further purification done by
crystallizing from hexanes.
S7
Yield: 5.38 g (33.8 mmol) of a pale liquid, 62 %. FTIR (KBr pellet, cm-1): 3333
(m, 15N-H), 2929 (m, Alkyl-H), 2860 (m, Alkyl-H), 1701 (s, C=O). 1H-NMR (400 MHz,
DMSOd6): δ (ppm) 7.08 (15N-H, J15N-1H = 92.0 Hz, JH-H = 5.6 Hz, 1H, dt), 3.50 (-CH3, 3H,
s), 2.95 (-CH2(CH2)4CH3, J = 6.4 Hz, 2H, pentet), 1.39 – 1.23 (-CH2(CH2)4CH3, 8H, m),
0.86 (-CH2(CH2)4CH3, J = 7.2 Hz, 3H, t). 13C-NMR (100 MHz, CDCl3): δ (ppm) 156.6
(J15N-13C = 26.5 Hz), 51.0, 40.2 (J15N-13C = 10.6 Hz), 31.0, 29.4, 25.9, 22.1, 13.9.
15
N-
NMR (40.5 MHz, CDCl3): δ (ppm) – 13.2. Mtheroetical = 161.1302, Msample = 161.1298, ΔM
= -0.4 mmass units (-2.48 ppm), C8H1715NO2.
15
N-Aniline hydrochloride:
15
NH2 HCl
To a 250 mL round bottom flask 1.64 g (10.78 mmol) of methyl
15
N-
hexylcarbamate was added with a stir bar. To the solid 50 mL of conc. HCl was added
and set to reflux for 12 hours. Following the reflux, the bulk of the acid was neutralized
with saturated solution of K2CO3 to a pH of 2. The aqueous solution was washed with
ethyl acetate and concentrated to a crude solid. Ethanol was added to extract the product
from the crude mixture of salts and inorganic solids were filtered. The product was
recovered by removing the ethanol reduced pressure evaporation and drying under high
vacuum.
S8
Yield 0.58 g (4.44 mmol) of a yellow solid, 41.0 %. 1H-NMR (400 MHz,
DMSOd6): δ (ppm) 10.43 (15N-H, 3H, b), 7.48 (Ar-H, J = 7.6 Hz, 2H, td), 7.41 – 7.38
(Ar-H, 3H, m).
13
C-NMR (100 MHz, DMSO d6): δ (ppm) 132.1 (JC-N = 8.4 Hz), 129.7
(J15N-13C = 1.5 Hz), 127.8, 123.2.
15
N-NMR (40.5 MHz, CDCl3): δ (ppm) Insoluble in
CDCl3. HRMS-ESI: Mtheroetical = 95.0622, Msample = 95.0625, ΔM = 0.3 mmass units (3.1
ppm), C6H715N.
15
N-(1-hexylamine) hydrochloride:
15
NH2 HCl
To a 250 mL round bottom flask 5.00 g (31.21 mmol) of methyl
15
N-
hexylcarbamate was added with a stir bar. To the solid 50 mL of conc. HCl was added
and set to reflux for 16 hours. Following the reflux, the bulk of the acid was neutralized
with saturated solution of K2CO3 to a pH of 2. The aqueous solution was washed with
ethyl acetate and concentrated to a crude solid. Ethanol was added to extract the product
from the crude mixture of salts and inorganic solids were filtered. The product was
recovered by removing the ethanol reduced pressure evaporation and drying under high
vacuum.
Yield 2.64 g (26.3 mmol) of a white solid, 84.0 %. 1H-NMR (400 MHz, CDCl3):
δ (ppm) 8.19 (15N-H, J15N-1H = 73 Hz, 3H, d), 5.46 (15N-H, J15N-1H = 88 Hz, 1H, d), 2.22 (CH2CH2(CH2)3CH3, J = 8.0 Hz, 2H, t), 1.64 (-CH2CH2(CH2)3CH3, J = 7.2 Hz, 2H, p),
1.38 – 1.30 (-CH2CH2(CH2)3CH3, 6H, m), 0.89 (-CH2CH2(CH2)3CH3, J = 7.2 Hz, 3H, t).
S9
13
C-NMR (100 MHz, CDCl3): 40.1 (J15N-13C = 4.6 Hz), 31.3, 27.7, 26.4, 22.6, 14.1. 15N-
NMR (40.5 MHz, CDCl3): δ (ppm) – 50.1. HRMS-ESI: Mtheroetical = 103.1258, Msample =
103.1242, ΔM = 0.4 mmass units (3.8 ppm), C6H1515N.
S10
III. Synthesis 15N-Enriched (Thio)Ureas:
The formation of
15
N-phenyl isothiocyanate was done by using the scheme
provided form Mays et al.5 The synthesis of non-symmetric (thio)ureas have been
previously reported.6-11 For convenience, the procedure consisted of added 1.0 equivalent
of iso(thio)cyanate to 50 to 150 mL of dichloromethane or chloroform and chilling the
solution in an ice bath under a nitrogen blanket. To the solution, labeled amine was added
and reaction was allowed to warm to room temperature and react of overnight. Once
complete, the solvent was removed via reduced pressure evaporation, crystallized from
ethanol, and vacuum dried.
15
N-(n-hexyl)-15N-(phenyl) thiourea (U-2):
S
15
N
H
15
N
H
A 100 ml round-bottom containing 15 mL of dry dichloromethane, 1.83 mL (2.75
g, 23.9 mmol, 3 eq.) thiophosgene, and stir bar was cooled in a ice bath. To the vessel, a
solution of 1.04 g (8.0 mmol, 1.0 eq.)
15
N-aniline HCl, 1.39 mL (1.03 g, 8.0 mmol, 1.0
eq.) DIPEA, and 10 mL of dichloromethane was added slowly, followed by 0.96 g (23.9
mmol, 3.0 eq.) of finely crushed NaOH. The reaction was allowed to warm to room
temperature and react overnight. The solvent and excess thiophosgene was vacuum
S11
striped and the isothiocyanate was purified via column chrom. (25 hexane:1
dichloromethane). Without further purification, the solvent was removed and the
iosthiocyanate was redissolved in dichloromethane. To the reaction vessel, a solution of
1.10 g (8.0 mmol, 1.0 eq.)
15
N-hexylamine HCl, 2.78 mL (2.06 g, 15.9 mmol, 2.0 eq.)
DIPEA, and 10 mL of dichloromethane was added and stirred at room temperature for 4
hours. The thiourea was purified by column chrom. (50 ethyl acetate: 50 hexane) and
dried under high vacuum.
Yield: 1.24 g (5.2 mmol) yellow solid, 65.6 %. FTIR (KBr pellet, cm-1): 3232 (s,
15
N-H str), 3064 (s, aryl-H), 2948 (m, alkyl-H), 2923 (m, alkyl-H), 1599 (m, C=C), 1537
(s, C=S). 1H-NMR (400 MHz, DMSOd6): δ (ppm) 7.74 (15N-H, J15N-1H = 94.8 Hz, 1H, d),
7.45 (Ar-H, J = 8.4 Hz, 2H, td), 7.32 (Ar-H, J = 6.4 Hz, 1H, td), 7.20 (Ar-H, J = 7.6 Hz,
2H, dd), 6.01 (15N-H, J15N-1H = 88.4 Hz, 1H, d), 3.62 (-CH2CH2(CH2)3CH3, J = 7.2 Hz,
2H, t). 13C-NMR (75 MHz, DMSOd6): δ (ppm) 180.2 (J15N-13C = 15.7 Hz, JC-N = 16.6 Hz),
139.4 (J15N-13C = 15.1 Hz), 128.6, 124.0, 122.9, 43.9 (J15N-13C = 11.4 Hz), 31.0, 28.4, 26.1,
22.1, 14.0. 15N-NMR (40.5 MHz, CDCl3): δ (ppm): 29.3, 18.9. HRMS-ESI: Mtheroetical =
239.1361, Msample = 239.1351, ΔM = -1.0 mmass units (-4.18 ppm), C13H2015N2S.
S12
15
N-(n-hexyl)-N’-(phenyl) urea (U-3):
O
15
N
H
N
H
Following outline procedure for non-symmetric ureas: 50 mL of Chloroform,
0.68 g (4.90 mmol, 1.0 eq) of 15N-(1-hexylamine) hydrochloride, 0.64 mL (0.700g, 5.88
mmol, 1.2 eq)
phenyl isocyanate, and 1.30 mL, (0.99 g, 9.79 mmol, 2.0 eq.)
triethylamine.
Yield: 0.71 g (3.22 mmol) white crystals, 66 %. FTIR (KBr pellet, cm-1): 3325 (s,
15
N-H), 3037 (w, aryl-H), 2958 (m, alkyl-H), 2927 (m, alkyl-H), 2854 (m, alkyl-H), 1635
(s, C=O), 1597 (m, C=C). 1H-NMR (400 MHz, DMSOd6): δ (ppm) 8.67 (N-H, 1H, s),
7.36 (Ar-H, J = 8.0 Hz, 2H, dd), 7.20 (Ar-H, J = 7.2 Hz, 2H, td), 6.67 (Ar-H, J = 7.6 Hz,
2H, td), 6.01 (15N-H, J15N-1H = 89.2 Hz, JH-H = 5.6 Hz, 1H, dt), 3.06 (-CH2CH2(CH2)3CH3,
J = 6.0 Hz, 2H, t), 1.41 (-CH2CH2(CH2)3CH3, 2H, m), 1.27 (-CH2CH2(CH2)3CH3, 6H, m),
0.87 (-CH2CH2(CH2)3CH3, J = 6.4 Hz. 3H, m). 13C-NMR (100 MHz, DMSOd6): δ (ppm)
155.1 (C=O, J15N-13C = 20.4 Hz), 140.6, 128.6, 120.9, 117.5, 93.9, 31.0, 29.7, 26.1, 22.1.
15
N-NMR (40.5 MHz, CDCl3): δ (ppm): -9.6. HRMS-ESI: Mtheroetical = 222.1619, Msample
= 222.1619, ΔM = 0 mmass units (0 ppm), C13H2215NNO.
S13
N-(n-hexyl)-15N’-(phenyl) urea (U-4):
O
N
H
15
N
H
Following outline procedure for non-symmetric ureas: 150 mL of Chloroform,
1.49 g (1.49 mmol, 1.1 eq) of 1-hexyl isocyanate, 0.97 mL (1.00g, 10.62 mmol, 1.0 eq)
15
N-aniline.
Yield: 1.20 g (5.42 mmol) white crystals, 51 %. FTIR (KBr pellet, cm-1): 3334 (s,
N-H), 3302 (s, N-H), 3037 (w, aryl-H), 2958 (m, alkyl-H), 2929 (m, alkyl-H), 2854 (m,
alkyl-H), 1633 (s, C=O), 1595 (m, C=C). 1H-NMR (400 MHz, DMSOd6): δ (ppm) 8.37
(15N-H, J15N-1H = 88.0 Hz, 1H, d), 7.37 (Ar-H, J = 6.8 Hz, 2H, dd), 7.22 (Ar-H, J = 7.2 Hz,
2H, t), 6.87 (Ar-H, J = 7.2 Hz, 2H, t), 6.10 (N-H, J = 5.6 Hz, 1H, t), 3.06 (CH2CH2(CH2)3CH3, J = 6.0 Hz, 2H, q), 1.41 (-CH2CH2(CH2)3CH3, 2H, m), 1.28 (CH2CH2(CH2)3CH3, 6H, m), 0.87 (-CH2CH2(CH2)3CH3, J = 6.8 Hz. 3H, t). 13C-NMR (75
MHz, DMSOd6): δ (ppm) 155.2 (J15N-13C = 19.7 Hz), 140.6 (J15N-13C = 15.7 Hz), 128.6,
120.9, 117.5, 39.1, 31.2, 29.8, 26.1, 22.1, 14.0.
15
N-NMR (40.5 MHz, CDCl3): δ (ppm)
7.4. HRMS-ESI: Mtheroetical = 222.1619, Msample = 222.1619, ΔM = 0 mmass units (0 ppm),
C13H2015NNO.
S14
N-(n-hexyl)-15N’-(n-hexyl) urea: (U-5):
O
15
N
H
N
H
Following outline procedure for asymmetric ureas: 50 mL of dichloromethane,
0.68 g (4.90 mmol, 1.0 eq) of
15
N-(1-hexylamine) hydrochloride, 0.86 mL (0.75 g, 5.88
mmol, 1.2 eq) 1-hexyl isocyanate, and 1.30 mL, (0.99 g, 9.79 mmol, 2.0 eq.)
triethylamine.
Yield: 0.95 g (4.15 mmol) white crystals, 85 %. FTIR (KBr pellet, cm-1): 3329 (s,
N-H), 2956 (m, alkyl-H), 2929 (m, alkyl-H), 2856 (m, alkyl-H), 1616 (s, C=O).
1
H-
NMR (400MHz, DMSOd6): δ (ppm) 5.69 (N-H, J = 4.0 Hz, 1H, t), 5.69 (15N-H, J15N-1H =
88.4 Hz, J1H-1H = 6.0 Hz, 1H, dt), 2.94 (-CH2(CH2)4CH3, J = 6.8 Hz, 4H, sextet), 1.33 –
1.23 (-CH2(CH2)3CH3, 16H, m), 0.86 (-CH2CH2(CH2)3CH3, J = 6.0 Hz. 6H, t). 13C-NMR
(100 MHz, CDCl3): δ (ppm) 159.0 (J15N-13C = 19.7 Hz), 40.7 (J15N-13C = 10.6 Hz), 40.7,
31.8, 30.5, 26.9, 22.8, 14.3. 15N-NMR (40.5 MHz, CDCl3): δ (ppm) – 12.5. HRMS-ESI:
Mtheroetical = 230.2245, Msample = 230.2250, ΔM = 0.5 mmass units (2.17 ppm),
C13H2815NNO.
S15
IV. Synthesis 15N-Enriched Carbodiimides:
The general procedure for dehydryaztion/desulfurization of ureas and thioureas
follow standard protocol previously reported.6-8 For convenience, the procedure consists
of the addition of 1.2 equivalents of triphenylphosphine dribromide to 10 mL of
dichloromethane in 250 to 500 mL round-bottom flask. The nitrogen blanket was placed
on the solution and cooled in an ice bath. Following cooling, 2.5 equivalent of
triethylamine was added slowly to the solution. To the activated reaction system, 1.0
equivalent of the urea was added in 4 portions over an hour and allowed to reactive for 4
to 8 hours. Following the reaction time, 250 mL of pentanes were added to precipitate
byproducts, which are filtered and removed. The solvent was removed via reduced
pressure evaporation and crude mixer was purified using pH 7-balanced silica gel with a
50 wt. % hexanes in ethyl acetate as the mobile phase.
S16
15
N-(n-hexyl)-15N’-(phenyl) carbodiimide (M-2):
15
N
C
15
N
10 mL of dichloromethane, 1.12 g (2.64 mmol, 1.2 eq.) triphenylphosphine
dibromide, 0.73 mL (0.56 g, 5.51 mmol, 2.5 eq.) triethylamine, and 0.49 g (2.20 mmol,
1.0 eq.) 15N-hexyl-15N’-phenylthiourea.
Yield: 0.24 g (1.18 mmol), colorless oil, 54 %. FTIR (KBr thinfilm, cm-1): 3062
(w, aryl-H), 3030 (w, aryl-H), 2929 (m, alkyl-H), 2858 (m, alkyl-H), 2110 (s,
15
N=C=15N), 1593 (m, C=C). 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.31 (Ar-H, J = 7.6
Hz, 2H, td), 7.11 (Ar-H, J = 6.5 Hz, 3H, td), 3.43 (-CH2CH2(CH2)3CH3, J = 8.0 Hz, 2H,
t), 1.71 – 1.66 (-CH2CH2(CH2)3CH3, 2H, m), 1.44 – 1.28 (-CH2CH2(CH2)3CH3, 6H, m),
0.91 (-CH2CH2(CH2)3CH3, J = 8.0 Hz, 3H, t).
13
C-NMR (100 MHz, CDCl3): δ (ppm)
140.8 (J15N-13C = 8.0 Hz), 129.3 (J15N-13C = 2.0 Hz), 124.5, 123.5, 123.4, 46.8 (J15N-13C =
2.0 Hz), 31.3, 26.4, 22.5, 14.0. GC-MS: Mtheroetical = 204, Msample = 204, C13H1815N2.
15
N-(n-hexyl)-N’-(phenyl) carbodiimide (M-3):
N
C
15
N
10 mL of dichloromethane, 1.60 g (3.79 mmol, 1.2 eq.) triphenylphosphine
dibromide, 1.05 mL (0.80 g, 7.91 mmol, 2.5 eq.) triethylamine, and 0.70 g (3.16 mmol,
1.0 eq.) 15N-(n-hexyl)-N’-(phenyl) urea.
S17
Yield: 0.39 g (1.92 mmol), colorless oil, 61 %. FTIR (KBr thinfilm, cm-1): 3066
(w, aryl-H), 3021 (w, aryl-H), 2929 (m, alkyl-H), 2858 (m, alkyl-H), 2119 (s, N=C=15N),
1593 (m, C=C).
1
H-NMR (300 MHz, CDCl3): δ (ppm) 7.27 (Ar-H, J = 4.5 Hz, 4H, td),
7.09 (Ar-H, 1H, m), 3.20 (-CH2CH2(CH2)3CH3, J = 7.2 Hz, 2H, t), 1.47 (CH2CH2(CH2)3CH3,
2H,
m),
1,26
CH2CH2(CH2)3CH3, J = 5.7 Hz, 3H, t).
(-CH2CH2(CH2)3CH3,
6H,
m),
0.87
(-
13
C-NMR (100 MHz, CDCl3): 141.1 (J15N-13C =
7.5 Hz), 129.5, 124.7, 123.7, 121.6, 47.1, 31.6, 31.5, 26.7, 22.7, 14.2.
N-(n-hexyl)-15N’-(phenyl) carbodiimide (M-4):
15
N
C
N
10 mL of dichloromethane, 2.29 g (5.42 mmol, 1.2 eq.) triphenylphosphine
dibromide, 1.57 mL (1.14 g, 11.30 mmol, 2.5 eq.) triethylamine, and 1.00 g (4.52 mmol,
1.0 eq.) N-hexyl-15N’-phenylurea.
Yield: 0.36 g (1.77 mmol) of clear liquid, 39%. FTIR (KBr thinfilm, cm-1): 3060
(w, aryl-H), 3030 (w, aryl-H), 2929 (m, alkyl-H), 2858 (m, alkyl-H), 2125 (s, 15N=C=N),
1593 (m, C=C). 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.31 (Ar-H, J = 8.0 Hz, 2H, td),
7.11 (Ar-H, J = 8.0 Hz, 3H, td), 3.43 (-CH2CH2(CH2)3CH3, J = 8.0 Hz, 2H, t), 1.74 –
1.65 (-CH2CH2(CH2)3CH3, 2H, m), 1.46 – 1.30 (-CH2CH2(CH2)3CH3, 6H, m), 0.9 (CH2CH2(CH2)3CH3, J = 8.0 Hz, 3H, t).
13
C-NMR (100 MHz, CDCl3): 140.8 (J15N-13C =
8.0 Hz), 129.3 (J15N-13C = 2.0 Hz), 124.5, 123.5, 123.4, 46.9, 31.4, 31.3, 26.5, 22.5, 14.0.
GC-MS: Mtheroetical = 204, Msample = 203, C13H1815NN.
S18
N-(n-hexyl)-15N’-(n-hexyl) carbodiimide (M-5):
N
C
15
N
10 mL of dichloromethane, 2.10 g (4.98 mmol, 1.2 eq.) triphenylphosphine
dibromide, 1.38 mL (1.05 g, 10.38 mmol, 2.5 eq.) triethylamine, and 0.95 g (4.15 mmol,
1.0 eq.) N-(n-hexyl)-15N’-(n-hexyl) urea.
Yield: 0.21 g (0.98 mmol) of clear liquid, 42 %. FTIR (KBr thinfilm, cm-1): 2951
(m, alkyl-H), 2925 (m, alkyl-H), 2925 (m, alkyl-H), 2117 (s, N=C=15N). 1H-NMR (400
MHz, CDCl3): δ (ppm) 3.20 (-CH2(CH2)4CH3, J = 6.8 Hz, 4H, t), 1.38 – 1.21 (CH2(CH2)4CH3, 16H, m), 0.90 (-CH2(CH2)4CH3, J = 7.2 Hz, 6H, t). 13C-NMR (100 MHz,
CDCl3): δ (ppm) 137.4 (J15N-13C = 9.9 Hz), 47.0, 31.6, 29.9, 26.7, 22.8, 14.2.
S19
V. Polymerization of 15N-Enriched Carbodiimides:
General Procedure for Polymerization: Polymerizations were done in a 20 mL
scintillation vials with an stir bar in a drybox containing a nitrogen atmosphere at 25 °C.
The vials and stir bars were oven dried overnight prior to use. The catalyst was added as a
solution in chloroform and polymerization was terminated after 5 days or when the stir
bar seized. The work up was done by dissolving the crude polymer in 1 mL of additional
chloroform and precipitated 250 mL of methanol and air dried. The precipitation was
done twice. Final drying was done under high vacuum.
poly(N-n-hexyl-N’-phenylcarbodiimide) (Poly-1):
The synthesis of Poly-1 has been previously reported.12
FTIR (KBr pellet, cm-1): 3059 (w, aryl-H), 3029 (w, aryl-H), 2927 (m, alkyl-H),
2858 (m, alkyl-H), 1626 (s, C=N), 1587 (m, C=C). 1H-NMR (400 MHz, CDCl3): δ (ppm)
6.60 (Ar-H, 5H, very board doublet), 1.58 – 0.40 (Alkyl-H, 13H, very board).
S20
poly(15N-n-hexyl-15N’-phenylcarbodiimide) (Poly-2):
15
F3C
O
N
15
N
H
n
0.14 g (0.71 mmol, 120 eq.),
15
N-(n-hexyl)-15N’-(phenyl) carbodiimide, 1.5 mg
(0.006 mmol 1.0 eq.) of Cat-1, and 0.50 mL dry Chloroform.
FTIR (KBr pellet, cm-1): 3059 (w, aryl-H), 3016 (w, aryl-H), 2954 (m, alkyl-H),
2929 (m, alkyl-H), 2858 (m, alkyl-H), 1612 (s, C=N), 1587 (m, C=C). 1H-NMR (400
MHz, CDCl3): δ (ppm) 6.60 (Ar-H, 5H, very board doublet), 1.58 – 0.40 (Alkyl-H, 13H,
very board). 15N-NMR (40.5 MHz, CDCl3): δ (ppm) 136.4 (15N=C, 1N), 15.5 (15N–C,
1N).
poly(15N-n-hexyl-15N’-phenylcarbodiimide) (Poly-3):
S21
15
F3C
O
N
N
H
n
0.36 g (1.77 mmol, 150 eq.) N-(n-hexyl)-15N’-(phenyl) carbodiimide, 3.00 mg
(0.0118 mmol 1.0 eq.) Cat-1, and 1.10 mL dry Chloroform.
Yield: 0.22 g (1.07 mmol) off-white solid, 60 %. FTIR (KBr pellet, cm-1): 3059
(w, aryl-H), 3022 (w, aryl-H), 2954 (m, alkyl-H), 2927 (m, alkyl-H), 2858 (m, alkyl-H),
1610 (m, C=N), 1585 (m, C=C). 1H-NMR (400 MHz, CDCl3): δ (ppm) 6.80 (Ar-H, 5H,
board doublet), 1.58 – 0.40 (Alkyl-H, 13H, very board). 15N-NMR (40.5 MHz, CDCl3): δ
(ppm) 137.3 (15N=C).
(R)- poly(15N-n-hexyl-N’-phenylcarbodiimide) ((R)-Poly-4):
S22
N
O
15
N
H
n
0.391 g (1.92 mmol, 120 eq.)
15
N-(n-hexyl)-N’-(phenyl) carbodiimide, 7.21 mg
(0.016 mmol 1.0 eq.) Cat-2, and 1.83 mL dry Chloroform
Yield: 0.221 g (1.09 mmol) off-yellow solid, 57 %. FTIR (KBr pellet, cm-1): 3059
(w, aryl-H), 3018 (w, aryl-H), 2954 (m, alkyl-H), 2927 (m, alkyl-H), 2858 (m, alkyl-H),
1626 (s, C=N), 1589 (m, C=C). 1H-NMR (400 MHz, CDCl3): δ (ppm) 6.60 (Ar-H, 4H,
very board doublet), 1.58 – 0.40 (Alkyl-H, 13H, very board).
CDCl3): δ (ppm) 15.4 (15N–C).
poly(15N-n-hexyl-N’-n-hexylcarbodiimide) (Poly-5):
S23
15
N-NMR (40.5 MHz,
15
N
N
H
F3C
O
15
N
m
N
n
0.49 g (2.32 mmol, 120 eq.) N-(n-hexyl)-15N’-(n-hexyl) carbodiimide, 4.9 mg
(0.0194 mmol, 1.0 eq.) of Cat-1 and 1.79 mL dry CHCl3.
Yield: 0.13 g (0.617 mmol) white solid, 27 %. FTIR (KBr pellet, cm-1): 2956 (m,
alkyl-H), 2927 (m, alkyl-H), 2856 (m, alkyl-H), 1637 (s, C=N). 1H-NMR (300 MHz,
CDCl3): δ (ppm) 4.10 (2H, board), 3.13 (2H, board singlet), 1.30 (12H, board doublet),
0.88 (6H, board singlet). 15N-NMR (40.5 MHz, CDCl3): δ (ppm) 132.9 (15N=C, 1N), 1.7
(15N–C, 1N).
S24
VI. 15N-NMR spectra and IR spectra of Polymers:
poly(N-n-hexyl-N’-phenylcarbodiimide) (Poly-1):
IR Spectra
S25
poly(15N-n-hexyl-15N’-phenylcarbodiimide) (Poly-2):
IR Spectra
15
N-NMR Spectra
S26
poly(N-n-hexyl-15N’-phenylcarbodiimide) (Poly-3):
IR Spectra
15
N-NMR Spectra
S27
(R)- poly(15N-n-hexyl-N’-phenylcarbodiimide) ((R)-Poly-4):
IR Spectra
15
N-NMR Spectra
S28
poly(15N-n-hexyl-N’-n-hexylcarbodiimide) (Poly-5):
IR Spectra
15
N-NMR Spectra
S29
VI. References:
(1)
Goodwin, A.; Novak, B. M. Macromolecules 1994, 27, 5520.
(2)
Tang, H. Z.; Lu, Y. J.; Tian, G. L.; Capracotta, M. D.; Novak, B. M. J. Am.
Chem. Soc. 2004, 126, 3722.
(3)
Zhang, Y. D.; Lin, C. J.; Li, Z.; Qin, L. Q.; Wen, H. L. J. Labelled Compd.
Radiopharm. 2010, 53, 183.
(4)
Huang, H. C.; Seid, M.; Keillor, J. W. J. Org. Chem. 1997, 62, 7495.
(5)
Mays, J. R.; Roska, R. L. W.; Sarfaraz, S.; Mukhtar, H.; Rajski, S. R.
ChemBioChem 2008, 9, 729.
(6)
Kennemur, J. G.; Clark, J. B.; Tian, G. L.; Novak, B. M. Macromolecules
2010, 43, 1867.
(7)
Kennemur, J. G.; Kilgore, C. A.; Novak, B. M. J. Polym. Sci., Part A:
Polym. Chem. 2011, 49, 719.
(8)
Kennemur, J. G.; Novak, B. M. Polymer 2011, 52, 1693.
(9)
Budhathoki-Uprety, J.; Novak, B. M. Polymer 2010, 51, 2140.
(10)
Budhathoki-Uprety, J.; Novak, B. M. Macromolecules 2011, 44, 5947.
(11)
Budhathoki-Uprety, J.; Peng, L.; Melander, C.; Novak, B. M. ACS Macro
Lett. 2012, 1, 370.
(12)
Tian, G. L.; Lu, Y. J.; Novak, B. M. J. Am. Chem. Soc. 2004, 126, 4082.
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